Goals / Objectives 1. Using an epidemiologic approach, investigate the role of whole grains, selected nutrients, other bioactive food components, and healthy dietary patterns in preventing the development of age-related conditions such as type 2 diabetes mellitus, cardiovascular disease, cancer, musculoskeletal disorders and age-related eye disease. 2. Determine the validity of biomarkers for whole grain intake, their use in assessing relationships between whole grain intake and disease risk, and the relationship between these biomarkers and insulin resistance phenotypes. 3. Using an epidemiologic approach, examine determinants of adherence to the recommended dietary patterns in the Dietary Guidelines for Americans (DGA) and the relation between adherence to these patterns and prevention of age-related weight gain, abdominal obesity, and related metabolic disorders such as inflammation, endothelial dysfunction and insulin resistance. 4. Using an epidemiologic approach, investigate safe upper limits for the dietary intake of folic acid. 5. Using an epidemiologic approach, determine relationships between dietary intake and nutrient status and the prevention of age-related cognitive decline in humans. 6. Using an epidemiologic approach, investigate the role of nutritional factors in limiting the cormorbidities such as CVD and premature mortality in individuals with chronic kidney disease (CKD).

Project Methods Many age-related conditions, such as cardiovascular disease, diabetes, dementia, cancer, musculoskeletal disorders and age-related eye disease, appear to have strong nutritional components. Improved nutrition through public health recommendations and interventions could have a tremendous impact on the economic and societal costs associated with these disabilities, but development of recommendations and interventions requires a greater understanding of the presumptive role that nutrition plays in delaying the onset of disease and disability. Epidemiologic methods applied to community-based investigations of aging populations provide a valuable tool to help meet this need. We will use these methods to address project objectives.

Progress 10/01/11 to 09/30/12

OutputsProgress Report Objectives (from AD-416): 1. Using an epidemiologic approach, investigate the role of whole grains, selected nutrients, other bioactive food components, and healthy dietary patterns in preventing the development of age-related conditions such as type 2 diabetes mellitus, cardiovascular disease, cancer, musculoskeletal disorders and age-related eye disease. 2. Determine the validity of biomarkers for whole grain intake, their use in assessing relationships between whole grain intake and disease risk, and the relationship between these biomarkers and insulin resistance phenotypes. 3. Using an epidemiologic approach, examine determinants of adherence to the recommended dietary patterns in the Dietary Guidelines for Americans (DGA) and the relation between adherence to these patterns and prevention of age-related weight gain, abdominal obesity, and related metabolic disorders such as inflammation, endothelial dysfunction and insulin resistance. 4. Using an epidemiologic approach, investigate safe upper limits for the dietary intake of folic acid. 5. Using an epidemiologic approach, determine relationships between dietary intake and nutrient status and the prevention of age-related cognitive decline in humans. 6. Using an epidemiologic approach, investigate the role of nutritional factors in limiting the cormorbidities such as CVD and premature mortality in individuals with chronic kidney disease (CKD). Approach (from AD-416): Many age-related conditions, such as cardiovascular disease, diabetes, dementia, cancer, musculoskeletal disorders and age-related eye disease, appear to have strong nutritional components. Improved nutrition through public health recommendations and interventions could have a tremendous impact on the economic and societal costs associated with these disabilities, but development of recommendations and interventions requires a greater understanding of the presumptive role that nutrition plays in delaying the onset of disease and disability. Epidemiologic methods applied to community-based investigations of aging populations provide a valuable tool to help meet this need. We will use these methods to address project objectives. Our research on nutrition and risk of obesity and chronic disease (Objective 1) included projects related to metabolic risk factors, inflammation, cardiovascular disease (CVD) and cancer. As part of our research on diet and metabolic risk factors, we observed that individuals with an index reflecting higher vitamin D status had less increase in fasting glucose concentrations as they aged. As part of our research on the relation between diet and inflammation, we demonstrated that individuals with greater levels of inflammation, based on higher levels of multiple blood biomarkers that reflect inflammation in a variety of tissues, were more than three times more likely to have inadequate blood levels of vitamin B6. As part of our research on diet and CVD, we showed that greater intake of the carotenoid lycopene, which is derived largely from consumption of tomato products, was associated with a 15 to 25% lower risk of CVD. As part of our research on the role of diet on cancer risk, we observed that the risk of esophageal squamous cell carcinoma, the sixth most common cancer in the world, was 60% lower among Iranian men and women who consumed a Mediterranean-style diet. Our progress on characterizing the role of nutrition in risk of age-related disease is crucial in identifying potential interventions aimed at maintaining health as we age. As part of our work of identifying biomarkers whole grain consumption (Objective 2), we conducted a whole wheat metabolic feeding study to determine the dose relationship between whole wheat consumption and circulating alkylresorcinol levels. Use of biomarkers, like alkylresorcinols, will ultimately help us to better characterize consumption of whole grains by Americans, and consequently, help us to better understand the benefits of whole grains on healthy aging. As part of the whole wheat feeding trial, we also conducted a pilot study to see if whole wheat consumption, which is rich in fibers that are believed to enhance the growth of beneficial gut bacteria, modified the types and proportions of gut bacteria (Objective 1). There is growing evidence that the types of gut bacteria may influence aspects of health from inflammatory bowel disease to weight gain. As part of our research on B vitamins and cognitive function (Objective 5), we have terminated enrollment and follow-up cognitive testing for our B vitamin intervention study, which is designed to examine the hypothesis that B vitamin supplementation is associated with less age-related cognitive decline, due to the premature termination of the parent trial on which our ancillary cognitive study was based. We have begun to explore the potential effects of B vitamin supplements on age-related cognitive changes using the data available to us from testing prior to the termination of the study. Our accomplishments related to this objective will help us understand the role of nutrition in preventing age-related cognitive decline. Accomplishments 01 Lycopene and tomato product intake reduce incidence of cardiovascular disease (CVD). The limited number of prior studies examining the relationship between CVD and lycopene intake, a carotenoid derived mainl from tomatoes, failed to show any benefits of lycopene intake in spite o experimental evidence suggesting the opposite. ARS-funded researchers JMUSDA-HNRCA at Tufts University, Boston, Massachusetts used repeated measurements of diet for up to ten years to characterize usual long-term intake of lycopene and tomato products in order to fill the gap in availability of longitudinal data. We observed that incidence of CVD wa 15-25% lower among those with the highest lycopene intakes compared to those with the lowest intakes; similar results were seen based on the intake of tomato products. Including more tomato products as part of a healthy diet pattern may provide added benefit against the development o CVD, which remains a major public health concern for Americans. 02 Better vitamin D status slows the age-related increase in fasting blood glucose (sugar) levels. There is a growing belief that poor vitamin D status is associated with a higher risk of type 2 diabetes, but there is little evidence to suggest that vitamin D effects pre-diabetic metabolic conditions related to the development of diabetes, such as impaired fasting glucose. To help address this gap in our knowledge, ARS-funded researchers at JMUSDA-HNRCA at Tufts University, Boston, Massachusetts examined the relation between vitamin D status using previously validate vitamin D score and increases in fasting plasma glucose concentrations among adults without type 2 diabetes. We observed that blood glucose levels among individuals with lower vitamin D scores, indicative of poor vitamin D status, were 50% greater than levels for those individuals who had high vitamin D scores after 7 years of follow-up. These findings suggest that a better vitamin D status might be one means to slow the ag related increase in fasting glucose levels resulting in lower risk of impaired fasting glucose, consequently helping to prevent the later development of type 2 diabetes.

Impacts(N/A)

Publications

Progress 10/01/10 to 09/30/11

OutputsProgress Report Objectives (from AD-416) 1. Using an epidemiologic approach, investigate the role of whole grains, selected nutrients, other bioactive food components, and healthy dietary patterns in preventing the development of age-related conditions such as type 2 diabetes mellitus, cardiovascular disease, cancer, musculoskeletal disorders and age-related eye disease. 2. Determine the validity of biomarkers for whole grain intake, their use in assessing relationships between whole grains intake and disease risk, and the relationship between these biomarkers and insulin resistance phenotypes. 3. Using an epidemiologic approach, examine determinants of adherence to the recommended dietary patterns in the Dietary Guidelines for Americans (DGA) and the relation between adherence to these patterns and prevention of age-related weight gain, abdominal obesity, and related metabolic disorders such as inflammation, endothelial dysfunction and insulin resistance. 4. Using an epidemiologic approach, investigate safe upper limits for the dietary intake of folic acid. 5. Using an epidemiologic approach, determine relationships between B- vitamin status, homocysteine levels, genetic mutations and the prevention of age-related cognitive decline in humans. 6. Using an epidemiologic approach, investigate the role of nutritional factors in limiting the cormorbidities such as CVD and premature mortality in individuals with chronic kidney disease (CKD). Approach (from AD-416) Many age-related conditions, such as cardiovascular disease, diabetes, dementia, cancer, musculoskeletal disorders and age-related eye disease, appear to have strong nutritional components. Improved nutrition through public health recommendations and interventions could have a tremendous impact on the economic and societal costs associated with these disabilities, but development of recommendations and interventions requires a greater understanding of the presumptive role that nutrition plays in delaying the onset of disease and disability. Epidemiologic methods applied to community-based investigations of aging populations provide a valuable tool to help meet this need. We will use these methods to address project objectives. Our research on nutrition and risk of obesity and chronic disease (Objective 1) included projects related to obesity, inflammation, diabetes, and CVD. As part of our research on weight gain and obesity, we showed that whole-grain intake was inversely associated with visceral adiposity, but that increasing consumption of refined grain appeared to negate the protective association between whole grains and visceral adiposity. As part of our research on diet and metabolic risk, we observed that an index reflecting higher vitamin D status was associated with a lower incidence of type 2 diabetes. Preliminary findings from our research on flavonoid intake and inflammation suggest that higher intakes of two subclasses of flavonoids, the flavonols and anthocyanidins, were associated with less inflammation. As part of our research on diet and CVD, we showed that a higher level of circulating homocysteine, a blood marker indicating lower vitamin B12 and folate status, was associated with increased risk of plaque formation in the carotid artery. Our progress on characterizing the role of nutrition in risk of age-related disease is crucial in identifying potential interventions aimed at maintaining health as we age. As part of our work of identifying biomarkers whole grain consumption (Objective 2), we measured blood alkylresorcinol levels in a group of healthy elderly individuals. Alkylresorcinols are unique chemicals found in whole wheat and rye and are believed to be useful as a marker of whole wheat consumption. In preliminary analyses based on theses alkylresorcinol levels, we demonstrated that they correlated well with self-reported whole grain intake and were inversely associated with BMI in healthy older adults, confirming observational data showing higher whole grain intake is associated with lower BMI. We also initiated a whole wheat metabolic feeding study to determine the dose relationship between whole wheat consumption and circulating alkylresorcinol levels. Use of biomarkers, like alkylresorcinols, will ultimately help us to better characterize consumption of whole grains by Americans, and consequently, help us to better understand the benefits of whole grains on healthy aging. As part of our research on B vitamins and cognitive function (Objective 5), we have stopped follow-up cognitive testing for our B vitamin intervention study, which is designed to examine the hypothesis that B vitamin supplementation is associated with less age-related cognitive decline, due to the premature termination of the parent trial on which our ancillary cognitive study was based. Our accomplishments related to this objective will help us understand the role of nutrition in preventing age- related cognitive decline. As part of our new objective (objective 6) on the role of nutritional factors in limiting the co-morbidities such as CVD and premature mortality in individuals with chronic kidney disease, we demonstrated that supplementation with folic acid, vitamin B12 and vitamin B6 was not effective at reducing the risk of cardiovascular disease in renal transplant recipients exposed to mandatory fortification of enriched cereal grain products. Accomplishments 01 Whole-Grain and Refined-Grain Intakes have Opposite Relationships with Visceral Fat. Given the emerging evidence that the visceral adipose tissue (VAT) compartment is more strongly related to metabolic risk factors than subcutaneous adipose tissue (SAT), ARS-funded researchers a JMUSDA-HNRCA at Tufts University, Boston, MA, examined the association o whole- and refined-grain intake on these body fat depots in a large population-based cohort of ambulatory adults to gain further insight int the relation between grain intake and cardiometabolic risk. They observed that increasing intakes of whole-grain intake was associated wi less VAT whereas increasing intakes of refined-grain intake was associat with more VAT; however, the association between higher whole grain intak and less VAT was not seen among those who consumed 4 or more servings pe day of refined grain. This research suggests that higher intakes of who grains may help limit the amount of harmful visceral adipose tissue, but that this beneficial effect of whole grains may be negated by consuming more 4 or more servings of refine grains per day. At this time the mechanism(s) by which whole and refined grains interact to influence VAT is unknown. 02 Higher Predicted Vitamin D Status is Associated with a 40% lower Risk of Type 2 Diabetes. The relation between vitamin D and bone health is well established, but there is accumulating evidence that vitamin D might hav other functions, including involvement in the development of type 2 diabetes (T2D). To further explore the potential benefits of improved vitamin D status on risk of developing T2D, ARS-funded researchers at JMUSDA-HNRCA at Tufts University, Boston, MA, examined the relation between predicted vitamin D status and risk of T2D in a large population based cohort of ambulatory adults, free of T2D. They demonstrated that individuals with the highest vitamin D status at baseline had a 40% lowe incidence of T2D over 7 years of follow-up than those with the lowest predicted vitamin D status. These findings suggest that maintaining optimal vitamin D status may be a strategy to help prevent the developme of T2D.

Impacts(N/A)

Publications

Progress 10/01/09 to 09/30/10

OutputsProgress Report Objectives (from AD-416) 1. Using an epidemiologic approach, investigate the role of whole grains, selected nutrients, other bioactive food components, and healthy dietary patterns in preventing age-related development of metabolic risk factors for type 2 diabetes mellitus, cardiovascular disease, cancer and musculoskeletal disorders. 2. Determine the validity of biomarkers for whole grain intake, their use in assessing relationships between whole grains intake and disease risk, and the relationship between these biomarkers and insulin resistance phenotypes. 3. Using an epidemiologic approach, examine determinants of adherence to the recommended dietary patterns in the Dietary Guidelines for Americans (DGA) and the relation between adherence to these patterns and prevention of age-related weight gain, abdominal obesity, and related metabolic disorders such as inflammation, endothelial dysfunction and insulin resistance. 4. Using an epidemiologic approach, investigate safe upper limits for the dietary intake of folic acid. 5. Using an epidemiologic approach, determine relationships between B- vitamin status, homocysteine levels, genetic mutations and the prevention of age-related cognitive decline in humans. 6. Using an epidemiologic approach, examine the relationships between vitamin D and fatty acid intakes and age-related eye diseases, including cataract and maculopathy. Approach (from AD-416) Many age-related conditions, such as cardiovascular disease, diabetes, dementia, cancer, musculoskeletal disorders and age-related eye disease, appear to have strong nutritional components. Improved nutrition through public health recommendations and interventions could have a tremendous impact on the economic and societal costs associated with these disabilities, but development of recommendations and interventions requires a greater understanding of the presumptive role that nutrition plays in delaying the onset of disease and disability. Epidemiologic methods applied to community-based investigations of aging populations provide a valuable tool to help meet this need. We will use these methods to address project objectives. Our research on nutrition and risk of obesity and chronic disease (Objective 1) included projects related to obesity, insulin resistance, metabolic syndrome, diabetes, and cardiovascular disease. As part of our research on weight gain and obesity, we showed that whole-grain and cereal fiber intakes were inversely related to percent total body and trunk fat mass and that better adherence to a Mediterranean diet was associated with a lower incidence of abdominal obesity. As part of our research on diet and metabolic risk, we observed that higher vitamin D status was associated with a lower risk of insulin resistance and diabetes and better adherence to a Mediterranean diet was associated with a lower incidence of metabolic syndrome and insulin resistance. As part of our research on diet and cardiovascular disease, we showed that a high glycemic index diet unfavorably affects triglycerides and HDL cholesterol, and that vitamin B6 status was inversely related to inflammation, an important cardiovascular disease risk factor. We completed the update of our food frequency flavonoid database for our project on flavonoid intake and cardiovascular disease risk and completed most of the statistical analyses for our project on plant-based diets, diet quality and cardiovascular disease risk. As part of our work of identifying biomarkers whole grain consumption (Objective 2), we measured blood alkylresorcinol levels. Alkylresorcinols are unique chemicals found in whole wheat and rye and are believed to be a potentially useful objective and quantitative marker of whole wheat consumption. These biomarkers will ultimately help determine consumption of whole grains by Americans. As part of our research on the Dietary Guidelines for Americans (DGA) (Objective 3), we showed that that better adherence to 2005 DGA is associated with a reduced progression of coronary artery atherosclerosis in women. This demonstrates that adherence the 2005 DGA is associated with a reduce risk of disease progression. As part of our research on safe upper limits of folic acid (Objective 4), we showed that unmetabolized folic acid, the synthetic form of the vitamin folate found in vitamin supplements and fortified foods, was detected in 50% of older Americans with folic acid intakes above 585 micrograms/day. We also showed that among older Americans with inadequate vitamin B12 status, the presence of circulating unmetabolized folic acid was related to lower scores on cognitive tests. This accomplishment helps us to better understand the basis for folic acid recommendations. As part of our research on B vitamins and cognitive function (Objective 5), we have completed recruitment and initiated baseline laboratory analyses. This accomplishment will help us understand the role of nutrition in age- related cognitive decline. For publications related to this project, see parent project #1950-51530- 009-00D. Accomplishments 01 Whole-Grain Intake and Cereal Fiber Are Associated with Lower Abdominal Adiposity. Foods high in dietary fiber may play an important role in regulating body weight. Few observational studies have examined the relationship between dietary fiber from different sources and body fat. ARS-funded researchers from Tufts University in Boston, MA examined the relation between grain intake (whole and refined), and measures of body fat. They observed that higher whole-grain and cereal fiber intakes were associated with a lower body mass index (a higher body mass index is a marker of overweight), percent total body fat, and percent trunk fat mas (trunk fat is a surrogate measure for abdominal fat mass, which is more strongly associated with risk of metabolic disorders than other fat depo . This research suggests that higher intakes of cereal fiber, particular from whole-grain sources, may be one means of limiting body fat mass, particularly in the abdominal region. 02 Plasma 25-Hydroxyvitamin D Is Associated with Insulin Resistance in Nondiabetic Adults. Insulin resistance is the main defect that characterizes the development of type 2 diabetes, but there is little information on the relationship between vitamin D status and insulin resistance. To advance our understanding of the role of vitamin D statu in the development of insulin resistance, ARS-funded researchers from Tufts University in Boston, MA examined the association between insulin resistance and plasma vitamin D levels. They observed that individuals with higher plasma vitamin D concentrations had less insulin resistance. These results suggest that maintaining optimal vitamin D status might be important for the prevention of type 2 diabetes. 03 Mediterranean-Style Dietary Pattern is Associated with a Reduced Risk of Metabolic Syndrome Traits and Incidence. There is evidence of the benef of the Mediterranean-style dietary pattern on disease risk in Mediterranean countries, but the health benefits of consuming a Mediterranean-style dietary pattern based on foods available in the American diet has not been demonstrated. Therefore, ARS-funded researche from Tufts University in Boston, MA examined the relation between consumption of a Mediterranean-style dietary pattern and insulin resistance, metabolic syndrome and its component risk factors (larger waist circumference, elevated blood glucose and triglyceride levels, and hypertension, and low HDL-cholesterol) in a population-based sample of adult Americans. They observed that individuals whose diets had greater conformity to the Mediterranean-style dietary pattern had smaller increases in waist circumference, blood glucose and triglyceride levels, and greater increases in HDL-cholesterol; were less likely to develop insulin resistance; and had a lower incidence of metabolic syndrome. These findings suggest that consumption of a diet consistent with the principles of the Mediterranean-style diet may be protective against developing metabolic syndrome, a potent risk factor for both diabetes an cardiovascular disease risk, in an American population.